The long-term objective of this Program Project is to develop a multiphased, preclinical laboratory system which can predict the effectiveness and safety of microbicides in clinical trials. A broad spectrum of sexually transmitted diseases (STDs) will be used including papillomavirus, HIV-1, HSV-2, T. pallidum, and Chlamydia. Microbicides will first be tested in vitro for mammalian cell toxicity and effectiveness against the STDs. However, the ultimate question is whether potential clinically useful microbicide can inhibit/destroy STD pathogens in the human vaginal environment with little or no toxicity to the vaginal wall. To this end, we have developed a unique model system in which xenografts of human vaginal tissue in immune deficient mice provide an environment similar to that which prevails in the human vagina. The microbicide which we shall initially evaluate include C31G, a surface active, two component agent. We shall evaluate structure/activity relationships, formulations, and delivery systems. Nonoxynol-9 will be included as a positive control. The laboratory systems which we shall refine in this project, should provide guidelines for the rapid, future development of more effective and safer microbicides.